Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

Abstract

In order to clarify the possible role of N-acetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD), we have carried out a meta-analysis testing the available evidence that NAC treatment may be effective in preventing exacerbations of chronic bronchitis or COPD and evaluating whether there is a substantial difference between the responses induced by low (≤ 600 mg per day) and high (> 600 mg per day) doses of NAC. The results of the present meta-analysis (13 studies, 4155 COPD patients, NAC n = 1933; placebo or controls n = 2222) showed that patients treated with NAC had significantly and consistently fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75, 95% CI 0.66-0.84; p < 0.01), although this protective effect was more apparent in patients without evidence of airway obstruction. However, high doses of NAC were also effective in patients suffering from COPD diagnosed using spirometric criteria (relative risk 0.75, 95% CI 0.68-0.82; p = 0.04). NAC was well tolerated and the risk of adverse reactions was not dose-dependent (low doses relative risk 0.93, 95% CI 0.89-0.97; p = 0.40; high doses relative risk 1.11, 95% CI 0.89-1.39; p = 0.58). The strong signal that comes from this meta-analysis leads us to state that if a patient suffering from chronic bronchitis presents a documented airway obstruction, NAC should be administered at a dose of ≥ 1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient.

FIGURE 1

Preferred reporting items for systematic reviews and meta-analyses flow diagram for the identification of studies included in the meta-analysis concerning the influence of N-acetylcysteine on chronic bronchitis or chronic obstructive pulmonary disease exacerbations.

FIGURE 2

Overall forest plot from meta-analysis carried out in all 13 selected studies a) assessing the relative risk of chronic obstructive pulmonary disease (COPD) exacerbations and b) subgroup analysis performed on seven randomised clinical trials in which inclusion criteria required diagnosis of COPD by pulmonary function testing. NAC: N-acetylcysteine.

FIGURE 3

Forest plot from meta-analysis carried out in 10 studies including low-dose N-acetylcysteine (NAC) treatment a) assessing the relative risk of chronic obstructive pulmonary disease (COPD) exacerbations and b) subgroup analysis performed on five randomised clinical trials in which inclusion criteria required diagnosis of COPD by pulmonary function testing.

FIGURE 4

Forest plot from meta-analysis carried out on four studies including high-dose N-acetylcysteine (NAC) treatment a) assessing the relative risk of chronic obstructive pulmonary disease (COPD) exacerbations and b) subgroup analysis performed on two randomised clinical trials in which inclusion criteria required diagnosis of COPD by pulmonary function testing.

FIGURE 5

Overall forest plot from meta-analysis carried out in 11 studies a) assessing the relative risk of adverse events; and subgroup analysis performed on studies including b) low and c) high doses of N-acetylcysteine (NAC).